Protein kinase A modulation of CaV1.4 calcium channels

The regulation of L-type Ca 2+ channels by protein kinase A (PKA) represents a crucial element within cardiac, skeletal muscle and neurological systems. Although much work has been done to understand this regulation in cardiac Ca V 1.2 Ca 2+ channels, relatively little is known about the closely related Ca V 1.4 L-type Ca 2+ channels, which feature prominently in the visual system. Here we find that Ca V 1.4 channels are indeed modulated by PKA phosphorylation within the inhibitor of Ca 2+ -dependent inactivation (ICDI) motif. Phosphorylation of this region promotes the occupancy of calmodulin on the channel, thus increasing channel open probability ( P O ) and Ca 2+ -dependent inactivation. Although this interaction seems specific to Ca V 1.4 channels, introduction of ICDI 1.4 to Ca V 1.3 or Ca V 1.2 channels endows these channels with a form of PKA modulation, previously unobserved in heterologous systems. Thus, this mechanism may not only play an important role in the visual system but may be generalizable across the L-type channel family. Phosphorylation of L-type calcium Ca V channels by protein kinase A is essential for several physiological events. Here, the authors show how this kinase regulates Ca V 1.4 activity, suggesting a general regulatory mechanism for all L-type calcium channels.